Bookman M A, Malmström H, Bolis G, Gordon A, Lissoni A, Krebs J B, Fields S Z
Fox Chase Cancer Center, Department of Medical Oncology, Philadelphia, PA 19111, USA.
J Clin Oncol. 1998 Oct;16(10):3345-52. doi: 10.1200/JCO.1998.16.10.3345.
Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel.
Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review.
One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths.
As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.
拓扑替康是一种拓扑异构酶I抑制剂，在一项多中心II期研究中对上皮性卵巢癌复发的女性进行了评估，这些女性此前接受过一或两种含铂和紫杉醇的治疗方案。
拓扑替康1.5mg/m²每日以30分钟静脉输注给药，连续5天，每21天为一个周期。入选标准包括二维可测量疾病、东部肿瘤协作组体能状态评分为2或更低，以及骨髓、肝脏和肾功能良好。疗效通过独立影像学评估。
139例患者接受了治疗；81%为铂耐药。62例患者接受过一种先前治疗方案，77例患者接受过两种先前治疗方案。9例患者无法评估疗效；然而，所有患者均纳入疗效分析。总缓解率为13.7%；铂耐药患者为12.4%，铂敏感患者为19.2%。27.3%的患者疾病稳定至少持续8周。缓解持续时间中位数和疾病进展时间分别为18.1周和12.1周。中位生存期为47.0周。82%的患者（34%的疗程）发生4级中性粒细胞减少，30%的患者（9%的疗程）发生血小板减少。6%的疗程发生感染并发症。非血液学毒性较轻。无药物相关的毒性死亡。
作为单一药物，拓扑替康对晚期上皮性卵巢癌女性患者有一定活性，这些患者在接受一或两种含铂和紫杉醇的先前治疗方案后病情进展或无反应。基于作用机制和耐受性，卵巢癌的一线治疗中需进一步研究联合治疗方案。
